cjm
Member
In which I put things places they weren't supposed to go...
Read dis first if ye ain't read it yet: IdeaLabs In Yer Eye!
~~~
BUT WHY? First yer eye, NOW YER NOSE?!
In short, my desire for an alternative delivery method of active substances is running into potential safety concerns. I'm pre-empting these concerns by shifting to yer nose, I mean da nose.
You might have your own reasons for wanting to try either eye or nasal administration of substances that work for you. Personally my gut is a wasteland from reckless supplementation and so many of my body processes seem to be vicious, unbreakable circles. I mentioned hypoxia in Yer Eye thread as a certain cause of my woes and Ray speaks about the importance of a "chain-breaker" in this context:
Solvent: Can pure saline be used? Yes. Intranasal saline alone is indicated for all sorts of minor and major ailments:
Are there other considerations for delivery? Maybe. I could add ammonia for less fuss at the border (blood-brain-barrier) but judging by the smell of my armpit sweat, I am replete in it. Really I don't think this solution needs any "encouragements" if you will, the nature of the nasal cavity/throat tissue is part of this system, critical to application:
Solute: After immediate results with Energin eye drops, that will be the active substance of choice for this pilot.
Bottle: I have an old Nasalcrom bottle (.88 oz, 100 metered sprays, more math in next section) at home that I'm not sure can be taken apart. If it can be, I will use that. I own a couple cheap defusers that are used for dispersing essential oils but it doesn’t seem practical to hold one by my face or light up a room with aerosol thiamine.
Dose:
Using a human-equivalent dose of 15% (I need a primer on this, may be way wrong) = 1.2 mg/kg, which is 97.2 mg for a 81 kg (~180 lbs) person. 100 mg total dose seems high through the nose, even if normal for an oral dose.
The doses there give a human range of 2.27 mg and 4.53 mg. Seems more reasonable for a pilot study.
This also jives with the 5.2 mg per spray of cromolyn sodium, a H2 anti-histamine [edit: I misspoke, it is actually called a "mast cell stabilizer"] and the active ingredient in Nasalcrom, which I tried when I was first looking into OTC remedies. (Zaditor [ketotifen] is an H2 anti-H eye-drop that was nice to use.) It’s a .88 oz bottle = ~26 mL = 26,000 uL. Nasalcrom says it contains 100 sprays, therefore each spray contains 260 uL or the equivalent of 5 drops.
If my original Tyronene eye drops contained ~.2 ug per drop, an equivalent nasal spray would be around 1 ug. My Progestene eye drops were denser, but in the ug range as well.
(I don’t know if there’s a good comparison between ophthalmic and intranasal doses, though, or at least I’m not sure how or where to compensate my variables to make a comparison.)
GIVEN ALL THAT, to get one full milligram of progesterone (using Progestene) in an intranasal spray of 260 ul, you need 62 or 63 drops into a total volume of 26 mL (520 drops).
Complications: Ethanol in this formulation is approaching 7%. I didn’t bother to check about the safety of ethanol in the nose until now:
OK I TRUST YOU J PHARM PHARMACEUT SCI
I’ll do the math on the dose of Energin per spray and put the damn thing in motion when I get home in a few hours.
Read dis first if ye ain't read it yet: IdeaLabs In Yer Eye!
~~~
BUT WHY? First yer eye, NOW YER NOSE?!
In short, my desire for an alternative delivery method of active substances is running into potential safety concerns. I'm pre-empting these concerns by shifting to yer nose, I mean da nose.
You might have your own reasons for wanting to try either eye or nasal administration of substances that work for you. Personally my gut is a wasteland from reckless supplementation and so many of my body processes seem to be vicious, unbreakable circles. I mentioned hypoxia in Yer Eye thread as a certain cause of my woes and Ray speaks about the importance of a "chain-breaker" in this context:
“It is often the deficiency of oxygen which unleashes the dangerous free-radical processes. Many substances can function as antioxidants/chain breakers: thyroxine, uric acid, biliverdin, selenium, iodine, vitamin A, sodium, magnesium, and lithium, and a variety of enzymes. Saturated fats work with antioxidants to block the spread of free-radical chain reactions. Age pigment is the brown material that forms spots on aging skin, and that accumulates in the lens of the eye forming cataracts, and in blood vessels causing hardening of the arteries, and in the heart and brain and other organs, causing their functions to deteriorate with age. It is made up of oxidized unsaturated oils with iron.” Iron’s Dangers
Solvent: Can pure saline be used? Yes. Intranasal saline alone is indicated for all sorts of minor and major ailments:
“The activity of nasal saline within the nasal cavity is mainly physical action. The saline will help to remove the excess mucus and improve mucociliary clearance. This will support nasal breathing in acute upper respiratory tract infections, including the common cold and rhinosinusitis.1 In addition to these cleaning effects, there may be other benefits coming from trace elements in sea water or intentionally added minerals to create so-called "enriched waters." According to some clinical studies, prophylactic use of moistening sprays can reduce the number of viral infections when taken regularly.2 The mechanisms behind this observation are not clear, but regular saline sprays may prevent drying out of the mucus layer and help to maintain the aforementioned natural defense mechanisms. Also, the action of trace minerals may play a role here. Nasal saline reduces swelling of the nasal mucosa and is therefore recommended as a nasal decongestant in response to an infection or allergy (hay fever). Lower volumes of saline administered as drops (often used for toddlers) or sprays will dilute the highly viscous mucus, which may be enough to improve or to re-start the mucociliary clearance mechanisms. Higher volumes of saline will actually wash away the largest part of mucus and debris from the nasal cavity. This is a recommended procedure for people suffering from chronic rhinosinusitis.3” Intranasal Saline: Can a Spray Per Day Keep the Doctor Away?
Are there other considerations for delivery? Maybe. I could add ammonia for less fuss at the border (blood-brain-barrier) but judging by the smell of my armpit sweat, I am replete in it. Really I don't think this solution needs any "encouragements" if you will, the nature of the nasal cavity/throat tissue is part of this system, critical to application:
“Intranasal drug administration is a noninvasive method of bypassing the blood-brain barrier (BBB) to deliver neurotrophins and other therapeutic agents to the brain and spinal cord. This method allows drugs that do not cross the BBB to be delivered to the central nervous system (CNS) and eliminates the need for systemic delivery, thereby reducing unwanted systemic side effects. Delivery from the nose to the CNS occurs within minutes along both the olfactory and trigeminal neural pathways. Intranasal delivery occurs by an extracellular route and does not require that drugs bind to any receptor or undergo axonal transport. Intranasal delivery also targets the nasal associated lymphatic tissues (NALT) and deep cervical lymph nodes. In addition, intranasally administered therapeutics are observed at high levels in the blood vessel walls and perivascular spaces of the cerebrovasculature.” Strategies for intranasal delivery of therapeutics for the prevention and treatment of neuroAIDS.
“Intranasal (i.n.) administration has emerged as a strategy to deliver therapeutics to the brain. Here, we compared i.n. and intravenous (i.v.) administration for testosterone. About 75% of the i.n. administered testosterone entered the blood. However, whole brain levels of testosterone were about twice as high after i.n. administration as after i.v. administration. About two-thirds of the testosterone entering the brain after i.n. administration did so by direct entry by nasal routes and the remainder indirectly by first entering the blood and then crossing the blood-brain barrier. All brain regions except the frontal cortex had higher levels of testosterone after i.n. administration than after i.v. administration, although the differences among brain regions varied much more for the i.n. route. The olfactory bulb, hypothalamus, striatum, and hippocampus had the highest levels after i.n. administration. The brain uptake pattern suggested a variety of distribution routes likely involving the cerebrospinal fluid, diffusion through brain tissue, and transport through nerve projections. Regional distribution patterns were similar after either i.n. or i.v. administration, suggesting that the dominant factor determining distribution/retention was the same for either route of administration. We conclude that the i.n. administration route delivers testosterone systemically and can target the brain, especially the olfactory bulb, hypothalamus, striatum, and hippocampus.” Delivery of testosterone to the brain by intranasal administration: comparison to intravenous testosterone.
Solute: After immediate results with Energin eye drops, that will be the active substance of choice for this pilot.
Bottle: I have an old Nasalcrom bottle (.88 oz, 100 metered sprays, more math in next section) at home that I'm not sure can be taken apart. If it can be, I will use that. I own a couple cheap defusers that are used for dispersing essential oils but it doesn’t seem practical to hold one by my face or light up a room with aerosol thiamine.
Dose:
“Mice received intranasal or intraperitoneal administrations of progesterone (8 mg/kg) at 1, 6, and 24 h post-MCAO.” Intranasal delivery of progesterone after transient ischemic stroke decreases mortality and provides neuroprotection.
Using a human-equivalent dose of 15% (I need a primer on this, may be way wrong) = 1.2 mg/kg, which is 97.2 mg for a 81 kg (~180 lbs) person. 100 mg total dose seems high through the nose, even if normal for an oral dose.
“The present study addresses the question of whether intranasally applied pregnenolone (IN-PREG) also has promnestic properties in the rat. We examined the effects of IN-PREG at doses of 0.187 and 0.373 mg/kg on memory for objects and their location on learning and retention of escape in a water maze, and on behavior on the elevated plus maze.” Promnestic effects of intranasally applied pregnenolone in rats
The doses there give a human range of 2.27 mg and 4.53 mg. Seems more reasonable for a pilot study.
This also jives with the 5.2 mg per spray of cromolyn sodium, a H2 anti-histamine [edit: I misspoke, it is actually called a "mast cell stabilizer"] and the active ingredient in Nasalcrom, which I tried when I was first looking into OTC remedies. (Zaditor [ketotifen] is an H2 anti-H eye-drop that was nice to use.) It’s a .88 oz bottle = ~26 mL = 26,000 uL. Nasalcrom says it contains 100 sprays, therefore each spray contains 260 uL or the equivalent of 5 drops.
If my original Tyronene eye drops contained ~.2 ug per drop, an equivalent nasal spray would be around 1 ug. My Progestene eye drops were denser, but in the ug range as well.
(I don’t know if there’s a good comparison between ophthalmic and intranasal doses, though, or at least I’m not sure how or where to compensate my variables to make a comparison.)
GIVEN ALL THAT, to get one full milligram of progesterone (using Progestene) in an intranasal spray of 260 ul, you need 62 or 63 drops into a total volume of 26 mL (520 drops).
Complications: Ethanol in this formulation is approaching 7%. I didn’t bother to check about the safety of ethanol in the nose until now:
“Co-solvents most used in intranasal formulations include glycerol, ethanol, propyleneglycol and polyethylene glycol and may be of the most importance since they are nontoxic, pharmaceutically acceptable and nonirritant to nasal mucosa.” Intranasal Drug Delivery: How, Why and What for?
OK I TRUST YOU J PHARM PHARMACEUT SCI
I’ll do the math on the dose of Energin per spray and put the damn thing in motion when I get home in a few hours.
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